Radiation shielding

ABSTRACT

Various configurations of shielding materials within shielding layers, such as for use in shielding radiation from implanted radioactive carriers, are discussed herein.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application a continuation of U.S. application Ser. No. 15/147,826,filed on May 5, 2016, which is a non-provisional of and claims thebenefit of U.S. Provisional Application No. 62/157,871, filed on May 6,2015, the entirety of which is hereby incorporated herein by reference.

FIELD

The inventions discussed herein generally relate to devices used inconjunction with radiation therapy.

BACKGROUND

Tumors in living organisms are highly variable in size, location andtheir amount of infiltration into normal tissues, the variability oftumors in general make them very difficult to treat with a one-size fitsall approach. Furthermore, the extent of tumors and/or void upondebulking are typically not known until presented in the operating room.Thus the options necessary to effectively treat a tumor or tumor bedneed to be quite diverse.

Brachytherapy involves placing a radiation source either into orimmediately adjacent to a tumor. It provides an effective treatment ofcancers of many body sites. Brachytherapy, as a component ofmultimodality cancer care, provides cost-effective treatment.Brachytherapy may be intracavitary, such as when treating gynecologicmalignancies; intraluminal, such as when treating esophageal or lungcancers; external surface, such as when treating cancers of the skin, orinterstitial, such as when treating various central nervous systemtumors as well as extracranial tumors of the head and neck, lung, softtissue, gynecologic sites, rectum, liver, prostate, penis and skin.

BRIEF DESCRIPTION OF THE DRAWINGS

The principles of the present invention will be apparent with referenceto the following drawings, in which like reference numerals denote likecomponents:

FIGS. 1A, 1B, and 1C are cross-sectional drawings illustrating a portionof patient tissue having radioactive carriers placed thereon.

FIG. 2A-2G illustrates various treatment surfaces with carriers placedthereon, and including one or more isolation sheets.

FIGS. 3A-3D are top views illustrating example dimensions and shapes ofisolation sheets.

FIGS. 4A-4I illustrate cross sections of isolation sheets, includingindications of example materials and material dimensions.

FIG. 5 illustrates an example of manufacturing an isolation sheet.

FIG. 6 illustrates an isolation sheet configured to provide backscatterproperties that return radioactive particles into a treatment area oftissue.

FIG. 7A illustrates three example shielding materials that may be usedin various embodiments of shielding layers and corresponding isolationsheets discussed herein.

FIGS. 7B-7L provide additional examples of isolation sheets that may bemanufactured for use in multiple dosimetric plans and/or may becustomize for a particular dosimetric plan.

FIG. 8 illustrates an example isolation sheet adjacent radioactive seedsin a substrate.

DETAILED DESCRIPTION

Although certain preferred embodiments and examples are disclosed below,inventive subject matter extends beyond the specifically disclosedembodiments to other alternative embodiments and/or uses and tomodifications and equivalents thereof. Thus, the scope of the claimsappended hereto is not limited by any of the particular embodimentsdescribed below. For example, in any method or process disclosed herein,the acts or operations of the method or process may be performed in anysuitable sequence and are not necessarily limited to any particulardisclosed sequence. Various operations may be described as multiplediscrete operations in turn, in a manner that may be helpful inunderstanding certain embodiments; however, the order of descriptionshould not be construed to imply that these operations are orderdependent. Additionally, the structures, systems, and/or devicesdescribed herein may be embodied as integrated components or as separatecomponents. For purposes of comparing various embodiments, certainaspects and advantages of these embodiments are described. Notnecessarily all such aspects or advantages are achieved by anyparticular embodiment. Thus, for example, various embodiments may becarried out in a manner that achieves or optimizes one advantage orgroup of advantages as taught herein without necessarily achieving otheraspects or advantages as may also be taught or suggested herein.

Overview

Tumors are difficult to eradicate surgically as their infiltrativenature often precludes microscopically complete resection without unduemorbidity or mortality. This local persistence of tumor cells may becontrolled if sufficient radiation can be delivered safely prior toregrowth and replication of the residual tumor cells. Debulking surgery,followed by radiation therapy may be used for local control of a tumor.Discussed herein are various systems, methods, and devices for use inconjunction with radiation therapy, such as to deliver (and to controldelivery of) radiation to a post-operative tumor bed.

Definitions

In order to facilitate an understanding of the systems and methodsdiscussed herein, a number of terms are defined below. The terms definedbelow, as well as other terms used herein, should be construed toinclude the provided definitions, the ordinary and customary meaning ofthe terms, and/or any other implied meaning for the respective terms.Thus, the definitions below do not limit the meaning of these terms, butonly provide exemplary definitions.

Tumor: an abnormal growth of tissue resulting from uncontrolled,progressive multiplication of cells. Tumors can be benign or malignant.

Tumor bed: an anatomical area of a patient (e.g., a human or othermammal) where a tumor exists (pre-operative tumor bed) and/or an areasurrounding a surgically removed tumor (post-operative tumor bed), suchas a cranial cavity from which a tumor was surgically removed. Evenafter surgical removal of a tumor, the remaining tumor bed of thepatient may include tumor cells.

Treatment area: an anatomical area that is targeted for delivery ofradiation, such as from one or more radiation delivery devices (e.g.,the carriers discussed below). A treatment area may include tissue belowand/or around a location where the radiation deliver device ispositioned, such as an anatomical area of a tumor or a tumor bed.

Treatment surface: an anatomical surface of a patient where a radiationdelivery device is to be placed to deliver radiation to a treatmentarea, such as the treatment surface itself and/or tissue below thetreatment surface. A treatment surface may be a portion of a tumor bedor any other anatomical surface. For example, if a tumor bed issurgically created, the treatment surface may include an entire exposedsurface of the tumor bed, a portion of such exposed surface, or theentire exposed surface of the tumor bed as well as a surrounding area oftissue.

Brachytherapy: radiation treatment in which the radiation deliverydevice is placed directly on and/or close to a treatment surface of thebody, such as directly on the surface of the body, within the body, orin a tumor bed. For example, brachytherapy may be intracavitary, such asin cranial or gynecologic malignancies; intraluminal, such as inesophageal or lung cancers; external, such as in cancers of the skin;and/or interstitial, such as in treatment of various central nervoussystem tumors as well as extracranial tumors of the head, neck, lung,soft tissue, gynecologic sites, rectum, liver, prostate, and penis.

Seed: a radioactive material that is configured for delivery ofradiation to a tumor and/or tumor bed. A seed may be in various shapesand sizes, such as cylinder, cone, sphere, pyramid, cube, prism,rectangular prism, triangular prism, and/or any combination of these orother shapes. While seeds are generally referred to herein ascylindrical, any other shape or size of seed may alternatively be usedin the various systems and methods discussed herein. Seeds may compriseany combination of one or more of multiple radioactive components, suchas Cs 131, Ir 192, I 125, Pd 103, for example. Seeds may include aprotective outer shell that partially or fully encases the radioactivematerial. Seeds are one form of radiation source. The term “radiationsource,” as used herein, generally refers to a radioactive seed (orother object that emits radiation), either alone (e.g., a seed) orembedded, or otherwise attached to, a carrier (e.g., a tile carrier withan embedded radioactive seed).

Carrier: a substrate that holds or contains a radioactive seed. Acarrier that contains one or more seeds is a radiation delivery device.Carriers may be configured for permanent implantation into a tumor bed,such as to provide radioactive energy to a treatment surface surroundingan area where a tumor has been removed in order to treat any remainingmalignant tissue. Carriers can be composed of various materials and takeon various shapes and sizes. Examples carriers, such as carriers havingvarious sizes, shapes, configurations, etc., are included in thefollowing patent and patent application, each of which is herebyincorporated by reference in its entirety and for all purposes:

-   -   U.S. patent application Ser. No. 14/322,785, filed Jul. 2, 2014,        now U.S. Pat. No. 8,876,684, entitled “Dosimetrically        Customizable Brachytherapy Carriers and Methods Thereof In The        Treatment Of Tumors,” and    -   U.S. patent application Ser. No. 14/216,723, filed Mar. 17,        2014, publication No. 2014/0275715, entitled “Dosimetrically        Customizable Brachytherapy Carriers and Methods Thereof In The        Treatment Of Tumors.”

Tile Carrier (also referred to as “Tile”): type of carrier that issubstantially planar and generally maintains a two-dimensional planargeometry when placed in a tumor bed. Depending on the material of thetile, though, the tile may be malleable such that the tile can bedeformed by bending in order to better conform to a tumor bed. Forexample, for tiles consisting essentially of collagen (and/or othermalleable materials), the tiles may be substantially bent as placed inor on a treatment surface (and/or when pressed against the treatmentsurface) to conform with the shape of the treatment surface, such as apost-operative tumor bed.

Gore Carrier (also referred to as “Gore”): type of carrier that is3-dimensional and conforms to the tumor bed while maintaining thegeometry necessary for an effective implant. In some embodiments, goresare initially planar and are reconfigured to take on a 3-dimensionalshape, such as to form a hemispherical surface that may be placed into asimilarly shaped tumor cavity.

Loader: a device that aids in placement of radioactive seeds incarriers, such as via injection of seeds into carriers. A loader, alsoreferred to herein as a “loading device,” may include multiplecomponents, such as to hold a carrier in place and guide a deliverydevice (e.g., a needle or injector) into the carrier in order to place aseed at a precise location in the carrier. U.S. patent application Ser.No. 13/460,809, filed Apr. 30, 2012, now U.S. Pat. No. 8,939,881,entitled “Apparatus For Loading Dosimetrically CustomizableBrachytherapy Carriers,” and U.S. patent application Ser. No.14/696,293, filed Apr. 24, 205, entitled “Apparatus and Method forLoading Radioactive Seeds Into Carriers,” which are each herebyincorporated by reference in their entirety for all purposes, describeseveral embodiments of loaders. As discussed further herein, loaders maybe operated manually, such as by human operators, or may be fullyautomated, such that carriers can be loaded with seeds using anautomated process. Alternatively, loaders may be configured to beautomated in part and require manual operation in part.

High Z Materials: any element with an atomic number greater than 20, oran alloy containing such materials.

Shielding Specifications (also referred to as a “Shielding plan”):attributes of one or more isolation sheets, such as attributes ofshielding layers and any other layers (e.g., collagen or other spacinglayer, adhesive layers, etc.) included in the isolation sheets, such asany combination of those attributes (also referred to herein as“characteristics”) of shielding material(s)s, shielding layer(s), and/orisolation sheet(s) that are discussed below. Shielding specificationsmay be in digital form (e.g., in an electronic data structure, such as adatabase or table), written form (handwritten by an oncologist orsurgeon or printed from a digital form), and/or may be developed and/orupdated without (or prior to) placement of the isolation sheet(s). Thus,shielding specifications may be developed in real-time based on clinicalneed and/or other patient characteristics.

Shielding specifications may be determined to best meet one or more ofmany clinical needs (and/or other shielding goals or requirements), suchas to provide one or more isolation sheets that:

-   -   shield radiation from one or radiation sources to result in a        directional therapeutic treatment area. Radiation sources, such        as carriers embedded with radioactive seeds, generally emit        radiation in an omnidirectional manner, such that all areas        around the radiation sources absorb radiation (possibly in        varying amounts depending on the shape, size, placement, etc. of        the radiation source). Shielding specifications may be set to        reduce the range of radiation by blocking radiation emit in        certain directions;    -   reduce risk of imaging distortion due to interference by the        shielding materials (or other components) of the isolation        sheets;    -   reduce risk of RF heating caused by energy from MRI or other        imaging devices, thereby reducing risk of further patient        injuries, such as burning, as a result of imaging;    -   provide a preferred (or required in some embodiments)        malleability of the isolation sheets, such as to allow placement        of the isolation sheets in irregularly shaped treatment areas;        and/or    -   reduce risk of deflection (e.g., movement) of the isolation        sheets (and/or individual shielding materials within the        isolation sheets) by energy from imaging devices, such as MRI.        Several of the potential risks and/or limitations noted above,        as well as others, associated with use of MRI with shielding        materials (such as in an isolation sheet), as well as other        implants and devices, are discussed in “MRI Bioeffects, Safety,        and Patient Management,” Chapter 16, by Frank G. Shellock, Ph.D.        and John V. Crues, III, M.D., Biomedical Research Publishing        Group, 7751 Veragua Drive, Playa Del Rey, Calif. 90293, accessed        Oct. 16, 2013, which is hereby incorporated by reference for all        purposes, including its teachings regarding potential risks        and/or limitations associated with use of MRI with medical        implants and devices. In some embodiments, shielding        specifications for isolation sheets may be determined or        modified based on other potential risks or limitations described        in this book.

Shielding Material: any material that restricts movement of radioactiveparticles, such as by absorbing, reflecting, and/or scatteringradioactive particles. The term “shielding,” as used herein, generallyrefers to any mechanism of preventing radiation from moving through andexiting a corresponding shielding material, such as by the shieldingmaterial absorbing, reflecting, or otherwise blocking the radiation.Shielding materials in various forms may be used in the variousembodiments discussed herein. For example, a shielding material may bein the form of a particle, wire, rod, cylinder, bar, sheet, liquid,solution, foam, or any other form in which a material having radiationabsorbing and/or reflecting properties is possible. A shielding materialprovides a shielding rate, which is generally an amount of shielding ofradioactive energy (that is emitted from one or more radiation sources),provided by the particular shielding materials. Similarly, a shieldinglayer comprising multiple shielding materials and an isolation sheethave associated shielding rates, which are dependent on the combinationof shielding (and possibly non-shielding) materials therein. For someapplications, such as based on clinical need, an isolation sheet thatprovides a shielding rate of 25%, 50%, 75%, 90%, 95%, 98%, or some othershielding percentage, may be desired. As discussed herein, materialcomposition, shape, size, dimensions, etc. may impact the shieldingabilities of a shielding material. For applications (e.g., based onclinical need) where a higher shielding percentage is desired than maybe provided by a single shielding material, multiple shielding materialsmay be used in combination, in one or more shielding layers or isolationsheets.

In some embodiments, shielding materials comprise high Z materials, suchas tantalum, gold, platinum, tin, steel, copper, aluminum, etc. (e.g., a0.05 mm to 0.2 mm thickness metallic foil). In other embodiments, anyother material that reduces penetration of radiation may be a shieldingmaterial. For example, a non-metallic, yet dense compound, may be usedalone (or in combination with a metallic material) as a shieldingmaterial. Such a non-metallic shielding material may advantageouslylessen the chance of 1) MRI artifacts, 2) deflection of the isolationsheet, and/or 3) MRI-induced heating, such as may be caused by currentloop induction and/or radio-frequency induced tissue heating that may becaused by metallic shielding materials. Depending on the particularnon-metallic material, thickness of the material may be larger than arequired thickness of a metallic shielding material, in view of thegeneral enhanced shielding abilities of metallic materials. Non-metallichigh density shielding materials may beneficially provide shielding ofnon-target tissues from radiation particularly in applications where MRIor other magnetic field exposure may be anticipated. Examples ofnon-metallic shielding materials include polyetheretherketone (PEEK),nanoparticles, polymeric nanoparticles, encapsulated nanoparticles,calcium carbonate, calcium phosphate, calcium sulfate, barium sulfate,zirconium dioxide, polymers and polymer hybrids of these and othermaterials. Shielding materials may be combined to form a compositeshielding material. For example, a metallic cylinder may be filled with(non-metallic) liquid calcium carbonate, in order to form a shieldingmaterial that better addresses one or more of the clinical needs of thepatient than a separate metallic cylinder and liquid calcium carbonateor a solid metallic rod.

Any reference herein to a shielding material, even if the examplereferences a particular metallic or non-metallic material (e.g., aparticular form of a particular material), could be implemented with anyother shielding material (e.g., a different form and/or differentmaterial) and/or combination of shielding materials. For example, agolden rod shielding material be replaced with a PEEK mesh shieldingmaterial that provides similar radiation absorption and/or reflectingproperties. Dimensions (e.g., width, height, radius, thickness, etc.) ofvarious shielding materials that provide the same radiation absorptionand/or reflective properties may vary from one material to another.

Shielding Layer: one or more shielding materials configured forplacement on or near radioactive sources (e.g., seeds) for reducingpenetration of radiation outside of a treatment area. A shielding layermay comprise discrete layers of one or more materials, such as a goldfoil sheet or a polymer sheet. In other embodiments, a shielding layermay include particles of high Z or non-metallic material that may beembedded within a shielding layer substrate (comprising a shieldinglayer material), such as collagen or other bio-compatible material. Forexample, a collagen shielding layer substrate may be embedded with oneor more shielding materials arranged in a configuration that providesshielding for a particular patient (e.g., based on a planned use ofradioactive carriers in treating the patient). For example, a shieldinglayer may include one or more rods, braids, hollow rods, tubules (ortubes), bars, dots (or spheres), trapezoids, or other shape, shieldingmaterials embedded in a shielding layer substrate, or adhered to oneanother without use of a shielding layer substrate.

Isolation Sheet: A single shielding layer or combination of multipleshielding layers, such as adhered to one another in a predeterminedconfiguration in order to provide desired radiation shielding, whilelimiting imaging artifacts. In some embodiments, isolation sheets mayinclude multiple shielding layers in a grid or mesh pattern, eitheralone or filled with, encapsulated by, or a combination of filled andencapsulated with, shielding materials, in various configurations and/orpatterns. The pattern of shielding materials in the one or moreshielding layers advantageously improves effectiveness of the isolationsheet in shielding radioactive energy, as well as ease of handling(e.g., malleability that allows placement in the treatment area in thedesired configuration) and/or imaging characteristics (e.g., reducesartifacts from shielding materials).

For some isolation sheets, the closer they are placed to the radiationsource, the more protection the one or more shielding layers of theisolation sheet will have, given the geometric dispersal pattern of theradiation. Additionally, thicker isolation sheets can provide moreeffective blocking of the transmitted energy. However, especially withmetallic shielding materials, thicker shielding layers (andcorresponding isolation sheets comprising such thicker shielding layers)may cause undesirable effects such as artifact, radiofrequency heating,or other issues. In addition, thicker isolation sheets may haveundesirable handling characteristics, including stiffness and bulk.Thus, in some embodiments, shielding layers may include smaller,thinner, segmented, braided, and/or discontinuous shielding materialsthat provide greater pliability and help alleviate these concerns,especially when multiple shielding layers are used in an isolationsheet. Many variations of shielding layers and isolation sheets arediscussed herein, but there are many other combinations of shieldingmaterials, patterns of placement of shielding materials within ashielding layers, quantities and/or relative alignment of multipleshielding layers within an isolation sheet, etc. that are possible basedon this disclosure. To the extent shielding materials provide shieldingthrough scattering or reflection of radiation, multiple shielding layersand/or multiple layers of shielding materials within a single shieldinglayer may provide a higher shielding rate, such as by subsequent layersabsorbing (or otherwise shielding) radiation remaining (e.g., scattered)from the previous layer, eventually reducing the energy to a suitablelevel.

Dosimetry: a process of measurement and quantitative description of theradiation absorbed dose (e.g., rad) in a tissue or organ.

Dosimetric Plan: a description of the prescribed dosimetry, such as fora particular patient, associated with a particular clinical condition,and/or for use in a particular surgical cavity, etc. For example, adosimetric plan may indicate position, quantity, radioactive strength,etc., for placement of radioactive carriers on a treatment surface of apatient, such as in view of characteristics of a tumor removed (orplanned for removal) from the patient. In some embodiments, dosimetricplans may include shielding specifications (or a “shielding plan), suchas characteristics of an isolation sheet (e.g., any of the variouscharacteristics associated with treatment materials, shielding layers,and/or isolation sheets discussed herein) to be used on a patient afterimplantation of the radioactive carriers according to the dosimetricplan. In other embodiments, the dosimetric plan for a patient may notinclude shielding specifications and, for example, may leavedetermination of the shielding specifications to another specialist,such as a surgeon that implements the dosimetric plan. Thus, theshielding specifications may be determined based on clinical need, evenin real-time as or after the prescribed radioactive carriers arepositioned on the treatment surface. Determining shieldingspecifications based on clinical need may better accommodate actualclinical condition of a patient that may be unknown and/or change aftercreation of a dosimetric plan, such as after removal of a tumor. In someembodiments, clinical need may be considered in order to increaseshielding around sensitive tissue areas (e.g., an optic nerve, vitalorgans, etc.), place isolation sheet(s) on scar tissue areas, resizeisolation sheet(s) to better fit a surgical cavity, and/or otherclinical conditional. In some embodiments, shielding specifications maybe determined based on a dosimetric plan in view of clinical need of thepatient at the time of insertion of the prescribed radiation sources.Any discussion herein of determining shielding specifications accordingto a dosimetric plan, which is one type of “treatment plan” specific toradiation therapy planning, refer additionally to determination of thosesame shielding specifications according to clinical need, such thatshielding specifications may be determined based on a dosimetric planand/or clinical need.

Therapeutic Index: relationship between an amount of therapeutic effectprovided by a therapeutic agent, such as one or more radioactive seedsin carriers, to an amount that causes toxicity. The therapeutic indexmay indicate a relative amount of healthy tissue (non-target tissue)receiving radiation (e.g., above a certain dosage level) compared to anamount of the target area (e.g., a tumor or tumor bed) receivingradiation. The therapeutic index may be a ratio of radiation deliveredto a treatment area (e.g., tumor or tumor bed) to radiation delivered toareas surrounding the treatment area. Thus, a higher therapeutic indexgenerally indicates better localization of radiation to the treatmentarea, sparing as much of the surrounding area from radiation aspossible. Accordingly, improving the therapeutic index may increaselocal control of tumors and/or decrease the morbidity of treatment.

Example Carriers

FIGS. 1A and 1B are cross-sectional drawings illustrating a portion ofpatient tissue 102 and 112 having tumor beds 104 and 114 therein,respectively. These tumor beds 104 and 114 may have been created by asurgical process, such as a tumor debulking process that removed tumorcells. For example, the tissue 102 or 112 may represent cranial tissueof a human (or other mammal) wherein the tumor beds 104 and 114 aresurgically created in order to remove one or more tumors from the brain(and/or surrounding areas) of the patient. Thus, the tissue 102 and 112may represent different types of material, such as bone, fatty tissue,brain tissue, etc. Any reference herein to “tissue” may reference to anytype of mammalian material, including bone, fatty tissue, brain tissue,etc.

In the example of FIG. 1A, four tile carriers 106 are illustrated asalready placed within the tumor bed 104. Placement of the tiles 106 inthe tumor bed 104 may occur in the surgical room, such as immediatelyafter a surgical procedure, or elsewhere at some time after the surgicalprocedure, such as in a separate procedure performed hours, days, orweeks later. In the embodiment of FIG. 1A, the tiles 106 are pliablesuch that they conform to the treatment surface, which is the non-planarouter surface of the tumor bed 104 in this example. In one embodiment,the tiles 106 may comprise collagen that provides such flexibility inconforming the tiles 106 to a nonplanar surface. In the example of FIG.1B, tiles 116 that are placed in tumor bed 114 of tissue 112 arecomprised of a non-pliable substrate, such as a polymer, that maintainsits substantially planar shape even when placed within the tumor bed114. For ease of discussion, tile carriers discussed herein areillustrated as being flexible, such as the tiles 106 in FIG. 1A.However, any other type of tile carrier, as well as other configurationsof carriers, such as gore, star, or dot carriers, may be usedalternatively. Thus, any discussion herein of a tile carrier or anyother particular carrier should be interpreted to also includeembodiments using other types of carriers, no carriers at all (e.g.,radioactive seeds could be placed in a tumor bed without first beingplaced in a carrier), and/or any other radiation delivery device.

In the examples of FIGS. 1A and 1B, the tiles 106 and 116 each include aradioactive seed embedded therein. As discussed in the related patentsand patent applications noted above, the radioactive seeds can havevarious shapes, sizes, and characteristics. In the examples discussedherein, radioactive seeds are illustrated as generally cylindrical, suchas the cylinders included in each of the tiles 106 and 116 of FIGS. 1Aand 1B. However, other shapes and sizes of seeds may be used in otherimplementations. In the examples discussed herein, radioactive seeds aresubstantially rigid, such that they maintain their shape within theirrespective carriers. Thus, as shown in FIG. 1A, even when the carriers106 near the bottom of the tumor bed 104 are deformed to better engagewith the treatment surface, the seeds therein retain their linearcylindrical shape. In other embodiments, seeds may be more pliable, suchthat they are somewhat malleable in taking on a shape of a specifictreatment surface. In the example of FIG. 1C, a tumor cavity is notpresent and, thus, the carriers 126 are placed on a substantially planartreatment area of tissue 122, such as a patient's skin covering theskull or other tissue.

In the examples of FIGS. 1A, 1B, and 1C radiation is delivered to thecorresponding treatment area by the radioactive seeds within thecarriers 106, 116, and 126, respectively. However, radiation from theseseeds may also extend to other areas of tissue that are outside of thedesired treatment area. For example, radiation emitted from top surfacesof the carriers may extend to surrounding tissue outside of thetreatment area, other portions of tissue that come near and/or contactthe treatment surface (e.g., the hand of a patient placed over the tumorbed 104), or even tissue of another person or animal, such as a spousethat lays near the treatment surface and, thus, receives radiation fromthe radioactive seeds. Accordingly, depending on placement of thecarriers, size and shape of treatment surface, radioactive seedintensity, and/or many other factors, the therapeutic index for use ofsuch carriers may be unnecessarily low. Discussed herein are variousshielding devices, systems, and methods, which are generally designed toimprove therapeutic index for delivery of radiation using brachytherapy.

Example Isolation Sheets

Disclosed herein are several embodiments of isolation sheets, which aregenerally any materials that are placed over and/or that are includedwithin radioactive carriers in order to provide radioactive shielding.As noted above, an isolation sheet may include a single shielding layer,which itself includes one or more shielding materials, or multipleshielding layers in various positional relationships to one another.Isolation sheets may improve a therapeutic index associated with adosimetry plan. Shielding materials used in isolation sheets may be mayinclude, for example, high-z material or alloy thereof, in variousforms, formed in shielding layers such as a foil, mesh, rods, cylinders,bars, dots, spheres, oriented strips, grid, embedded, sprayed,bio-adhered, or an on-lay in or on a substrate, such as one or morelayers of collagen. While specific shapes, material compositions,properties, etc. are disclosed herein with reference to various exampleisolation sheets, variations on these examples are anticipated.

In one embodiment, a shielding apparatus comprises a collagen substrateand a plurality of shielding materials embedded in the collagensubstrate, the shielding materials each comprising a high-z material,wherein the shielding materials are positioned within the collagensubstrate to match positions of a corresponding plurality of radiationsources arranged according to a dosimetric plan, at least some of theradiation sources arranged with gaps between the at least some of theradiations sources and adjacent of the plurality of radiation sources.In some embodiments, when the apparatus is placed on the plurality ofradiation sources, each of the shielding materials provides substantialshielding of radiation emitted by a corresponding radiation source andreduced shielding of radiation from other of the plurality of radiationsources, and gaps between respective shielding materials provide lessdistortion of magnetic energy than the shielding materials.

In some embodiments, gaps comprise collagen of the collagen substratebetween shielding materials. In some embodiments, substantial shieldingshields more than 80% of radiation. In some embodiments, reducedshielding shields less than 50% of radiation. In some embodiments, theone or more shielding materials are formed in the shape of rods,cylinders, or spheres.

In some embodiments, the dosimetric plan indicates x*y radiation sourcesarranged in x rows and y columns, and the collagen substrate is embeddedwith x*y shielding materials in x rows and y columns. In someembodiments, the dosimetric plan indicates a gap distance betweenadjacent radiation sources in each of the x rows, and the shieldingmaterials in each of the x rows are spaced apart by the gap distance. Insome embodiments, the dosimetric plan indicates a second gap distancebetween adjacent radiation sources in each of the y columns, and theshielding materials in each of the y columns are spaced apart by thesecond gap distance.

In some embodiments, the dosimetric plan indicates an irregulararrangement of the plurality of radiation sources, and the shieldingmaterials are positioned in the same irregular arrangement in thecollagen substrate.

In some embodiments, the shielding apparatus is sufficiently malleableto be formed into a substantially hemispherical shape within acorresponding substantially hemispherical cavity, while in otherembodiments, the shielding apparatus is configured for attachment oneither side of a substantially hemispherical cavity such that anair-filled void is formed between a bottom of the hemispherical cavityand the formed into a substantially hemispherical shape within acorresponding hemispherical cavity.

In some embodiments, the collagen substrate is adhered to abio-compatible material.

FIG. 2A illustrates a tumor cavity having four carriers, each embeddingone or more radioactive seeds, placed therein. In this embodiment, thecarriers are pliable such that they substantially engage the treatmentsurface. In this example, a thin isolation sheet 202 comprising a singleshielding layer is positioned on (or near) the carriers within the tumorbed and partially extending outside of the tumor bed. For example, theisolation sheet 202 may be pressed down into the tumor bed manually (bya surgeon's fingers, hands, or a surgical tool). In some embodiments,the isolation sheet 202 may be adhered to the carriers using an adhesiveproperty that is inherent to the carrier material and/or a separateadhesive. As noted above, certain carrier materials may have an inherentstickiness that adheres the carriers to the isolation sheet 202. Forexample, collagen carriers may adhere to the isolation sheet 202 (and/ortissue of the treatment surface on the opposing side) to varyingextents, depending on moisture on the isolation sheet 202 and/orcarriers.

FIG. 2B illustrates the tumor cavity again having four carriers embeddedtherein, but now with two thicker isolation sheets 204 (each comprisinga single shielding layer and/or multiple stacked shielding layers)overlaid thereon to provide radiation shielding (and to improvetherapeutic index). In other embodiments, a single thicker isolationsheet may be used. Similar to discussion above with reference to FIG.2A, the isolation sheets 204 may be placed on or near the carriers (e.g.inserted into the tumor cavity or covering an opening of the tumorcavity) in various matters and may be adhered to the carriers (eitherbefore or after insertion onto the treatment surface) in certainembodiments.

FIG. 2C illustrates an isolation sheet 206 that is adhered to carriersprior to insertion into a tumor bed. Depending on the embodiment, theisolation sheet 206 may be adhered using various adhesives, such as amedical grade adhesive. In this embodiment the isolation sheet 206 maymaintain attachment to the carriers better than when adhered within atumor cavity.

FIG. 2D illustrates one of the isolation sheets 204 placed in a tumorcavity to cover two radioactive carriers in order to provide shieldingof radiation from those carriers. In this example, a separate isolationsheet is placed directly on adjacent tissue (tissue outside of thetreatment area), such as to reduce or prevent radiation from enteringthe surrounding area. For example, in the tumor cavity of FIG. 2D, thetumor may have been entirely and/or primarily on the right side of theresultant tumor cavity, such that radioactive carriers are placed onlyon that side. However, in order to increase the therapeutic index of apost-operative radiation treatment plan, an isolation sheet can also beplaced nearby the radioactive carriers on non-treatment tissue in orderto shield that surrounding tissue from radioactivity.

In a similar way as the isolation sheet in FIG. 2D is placed directly ontissue outside of the treatment surface, in some embodiments a shieldingmaterial may be placed directly on such tissue and/or on radioactivecarriers in place of an isolation sheet. Any discussion herein of anisolation sheet similarly could include a shielding material that is notformed into an isolation sheet, but is rather applied directly to thetreatment surface or area adjacent to the treatment surface. Forexample, calcium phosphate (e.g., that is 95% resorbed in 26-86 weeks)or Calcium Sulfate (that resorbs in 4-12 weeks) may be provided as aninjectable paste such that a layer could be “painted” where needed toprovide shielding. Such a shielding material may be advantageously usedwhere an isolation sheet may not be practicable, such as extradural deepto suture lines. Such isolation materials may provide a bone-graftanalog, as discussed in “Bone-graft substitutes in orthopaedic surgery,”by Jahangir et al. (Published January, 2008 and available for downloadat http://www.aaos.org/news/aaosnow/jan08/reimbursement2.asp), which ishereby incorporated by reference in its entirety and for all purposes.

FIG. 2E illustrates four radioactive carriers 126 placed on a treatmentsurface that is substantially flat, above a treatment area of tissue122. As discussed elsewhere herein, isolation sheets may be applied toany treatment surface, whether substantially hemispherical, irregularlyshaped, substantially planar, or any other shape. In the example of FIG.2E, an isolation sheet 208 (which may include any shielding layer orcombination of shielding layers discussed herein, such as thosediscussed with reference to FIG. 4) is selected for placement atop theradioactive carriers 126.

In the example of FIG. 2F, an isolation sheet 210 is adhered to carriers128 prior to placement on a treatment area of tissue 122. As discussedelsewhere herein, the carriers 128 may be adhered to the isolation sheet210 via a separate adhesive compound or material, or via adhesiveproperties of one or more of the isolation sheet 210 and/or carriers128.

In the example of FIG. 2G, an isolation sheet 220 is placed over atreatment surface such that it is not directly contacting the carriers(except possibly end portions of the end carriers). Positioning anisolation sheet in this manner may be easier for the surgeon (thanmanipulating an isolation sheet into an irregular shaped cavity), lesspainful for the patient, and/or may provide similar amounts (or at leastsufficient amounts) of radiation shielding as an isolation sheet that ismanipulated into a tighter fit within a surgical cavity, such as in theexample of FIG. 2A. In applications where the treatment area is apatient's brain, this isolation sheet placement may be referred to asextracranial, denoting its placement outside of the cranium. Suchextra-cavity placement of isolation sheets is possible with any of theisolation sheets discussed herein. In some embodiments, extra-cavityplacement allows thicker and/or more shielding materials, whichgenerally cause more rigidity of the isolation sheet, to be used andmore easily positioned outside the surgical cavity.

FIGS. 3A-3D are top views illustrating example dimensions and shapes ofisolation sheets. The illustrated sizes and shapes are examples only—anyother shapes or dimensions are contemplated by this disclosure.Thicknesses of these example isolation sheets are not illustrated inthese figures, but example thicknesses and materials of isolation sheetsare illustrated in FIG. 4. Thicknesses of these example isolationsheets, which each include one or more shielding layers (which eachinclude one or more shielding materials, such as in a shielding layersubstrate), range from 0.05 mm to 8 mm in thickness, or maybe eventhicker (e.g., 10-20 mm) in other applications. Depending on theembodiment, and as illustrated in the examples herein, thicknesses ofisolation sheets may differ from thicknesses of the underlying carriers.For example, the carrier may have a thickness of 4 mm, while anisolation sheet applied to that carrier may have a thickness of only 1mm. Of course, any other combination of carrier and isolation sheetthicknesses are contemplated herein. Any of the isolation sheetsillustrated herein, including those in FIGS. 3A-3D may have anythicknesses, materials, and/or other characteristics discussed herein,such as those in FIG. 4.

In the example of FIG. 3A, a square isolation sheet having sides of alength from 1-5 cm is shown. For example, the isolation sheet may havesides that are each one centimeter. In other embodiments, a similarisolation sheet may be rectangular, such as having dimensions of 1 cm×5cm.

The example of FIG. 3B is a circular isolation sheet having a diameterof between 8-25 mm. Thus, example circular isolation sheets may havediameters of 10 mm, 15 mm, 20 mm, 25 mm, etc.

The example isolation sheet of FIG. 3C is a 5 cm×5 cm isolation sheetthat includes trim lines at one centimeter intervals. As noted elsewhereherein, isolation sheets may comprise materials (e.g., shieldingmaterials and/or substrate materials) that allow adjustment of size ofthe isolation sheet and/or creation of multiple smaller isolation sheetsfrom a single sheet. For example, an isolation sheet may be trimmedusing scissors, razor blade, knife, or similar cutting implement, tocreate a custom shaped isolation sheet, such as the irregularly shapedisolation sheet illustrated in FIG. 3D, which may be created by cuttingthe example isolation sheet of FIG. 3C.

Using the trim lines in the example of FIG. 3C, a user can accuratelycreate multiple isolation sheets having dimensions anywhere between 1cm-5 cm on either side. For example, a user could create four 1 cm×5 cmisolation sheets, two 2 cm×5 cm isolation sheets, or sixteen 1 cm×1 cmisolation sheets from the isolation sheet of FIG. 3C. In otherembodiments, trim lines may be placed at different intervals. In oneembodiment, trim lines may be generated by a dosimetric planningsoftware, such as the software discussed in U.S. patent application Ser.No. 15/017,461, entitled “Radioactive Implant Planning System andPlacement Guide System,” filed on Feb. 5, 2016, which is herebyincorporated by reference in its entirety. For example, in order toachieve a maximum therapeutic index, a custom shaped isolation sheet ormultiple isolation sheets may be determined by software and implementedby the user. In one embodiment, the software generates a printout of thetrimming pattern that can be overlaid on an isolation sheet so that theprinted trimming pattern as well as the isolation sheet thereunder canbe simultaneously trimmed in order to achieve the calculated isolationsheet size, shape, pattern, etc.

FIGS. 4A-4I illustrate cross sections of isolation sheets, includingindications of example materials and material dimensions. The isolationsheets are illustrated such that the bottom surface of each isolationsheet is placed onto (or near, such as in an extra-cavity placement)radioactive carriers. For example, the collagen layers in FIGS. 4A and4B are configured for placement onto radioactive carriers, with theshielding layer separated from the radioactive carriers by collagen.Isolation sheets of any shape or size, such as those discussed abovewith reference to FIG. 3, for example, may include shielding andnon-shielding layers similar to those illustrated in one or moreexamples in FIGS. 4A-4I, or combinations of layer components or layerthicknesses. In many embodiments, one or more layers of collagen, orsome other bio-compatible spacing material, may be used in conjunctionwith a shielding layer in order to provide distance between theradioactive materials in carriers and the shielding layers of anisolation sheet. Depending on characteristics of shielding materials,such as radiation shielding ability, replacement of a shielding layer bya shielding layer having a different shielding material may necessitateuse of the thicker (or thinner) shielding layer in order to achieve thedesired shielding goals (e.g., a minimum radiation shielding). Forexample, a high-z metal foil shielding layer of thickness 0.05 mmprovides higher radiation shielding than a non-metallic polymershielding layer of thickness 0.05 mm. Thus, to maintain similarradiation shielding with the non-metallic shielding layer may require athickness of 2 mm or more.

The examples of FIGS. 4A-4D include shielding layer comprising asubstantially uniform composition, such as a foil or polymer sheet of ashielding material. FIGS. 4E-4H include shielding materials that areinterspersed within a shielding layer substrate, such as high Z or othershielding materials that may be interspersed within a collagen layer.FIG. 4I illustrates an isolation sheet having a combination of a uniformcomposition shielding layer (e.g., a high Z metal foil layer) and adispersed composition shielding layer (e.g., small fragments of a densenonmetallic material interspersed within a collagen layer), along with acollagen layer on each side of the shielding layers.

Any examples herein of a shielding layer may include a uniformcomposition and/or a dispersed composition of shielding materials withina shielding layer substrate, even where specific other examples ofshielding layers are discussed. As noted elsewhere, layers of shieldinglayers discussed herein may be adhered using a separate adhesivematerial, by properties inherent in one or more of the layers (such aswetted collagen, for example), or may not be adhered together (e.g.,they may be placed adjacent to one another, but not adhered to oneanother). Thus, any discussion of shielding layers of an isolation sheetherein that does not mention adhesives may be modified to includeseparate adhesive materials and/or layers.

The appropriate combination of an absorptive material, such as collagen,and a reflective material, such as a metallic foil, to include in ashielding layer and/or multiple shielding materials, spacing materials,etc. of a shielding layer and/or an isolation sheet including multipleshielding layers, may be incorporated into a dosimetric plan for aparticular radiation treatment. For example, if a dosimetric planbenefits from radiation being reflected back towards the treatment area,a layer of collagen separating the carrier(s) and the reflectivematerial may be minimal or zero (e.g., zero—2 mm), while if absorptionof radiation from the carrier(s) is more desirable, a larger absorptivelayer may be implemented, such as a 10-30 mm layer of collagenunderneath a reflective shielding layer (or without a reflectivematerial layer). In some embodiments, multiple shielding layers and/orisolation sheets having different combinations of absorptive andreflective materials may be used in a single treatment plan, such thatradiation from certain carriers within the treatment plan is primarilyreflected back towards a treatment area, while radiation from othercarriers within the treatment plan is primarily absorbed by the adjacentisolation sheets.

In the example of FIG. 4A, the isolation sheet includes a singlecollagen layer and a shielding layer, such as comprising a uniformcomposition shielding material having a high Z material and/or a densenonmetallic material. Similarly, the isolation sheet in the example ofFIG. 4B includes a collagen material having a thickness of between1.0-10 mm combined with a shielding layer having a thickness of between0.05-2.0 mm. The example isolation sheet of FIG. 4C includes twocollagen layers that are configured to separate radioactive carriersfrom a shielding layer. In this embodiment, the multiple collagen layersmay be used in view of an increased availability, reduced cost, and/orother factors, of a thinner collagen layer than compared to a samethickness of a single collagen layer. In the example of FIG. 4C, each ofthe collagen layers has a thickness between 1.0-10 mm and the shieldinglayer has a thickness of between 0.05-2.0 mm. In one embodiment, each ofthe collagen layers has a same thickness, but in other embodimentscollagen layers of different thicknesses may be used. The example ofFIG. 4D illustrates an isolation sheet having an adhesive layerconfigured for attachment to radioactive carriers, such as to adhere theisolation sheet to the radioactive carriers before placement on atreatment surface or in order to adhere the isolation sheet to theradioactive carriers that are already positioned on the treatmentsurface. In this specific example, the adhesive layer having a thicknessof between 0.1-1.0 mm is adhered to a collagen layer having a thicknessof between 1.0-10 mm, which is adjacent to a shielding layer having athickness of between 0.05-2.0 mm, and finally a collagen layer having athickness of between 0.4-2.0 mm.

In the examples of FIG. 4E-4H, shielding layers are shown with variousshielding materials, which may include fragments, particles, pieces,and/or solutions, of high Z and/or nonmetallic materials, that areinterspersed within a shielding layer substrate. For example, theshielding layer substrate may be a collagen or similar bio compatiblematerial with suitable properties that is capable of holding orincorporating a shielding materials, such as particles of a high Zmaterial (e.g., an alloy, nanoparticle or mixture thereof) and/or anon-metallic high density material (e.g., calcium carbonate, calciumsulfate, barium sulfate, zirconium dioxide, polymers and polymer hybridsof these and other materials as may best fit the need). Such shieldingmaterials may advantageously provide increased tumor bed conformation(e.g., in view of the flexible nature of collagen and similarsubstrates) and/or improved intraoperative handling properties overuniform composition shielding materials alone.

Depending on embodiment, the shielding materials may be introduced intothe shielding layer substrate, e.g., a biocompatible substrate, byinfusion, soaking, suffusion, pressure inducement, absorption,electroporation, lypholization or other means on or into the latticestructure of, within, or between the interstices of the substrate, inorder to form a shielding layer. For example, a collagen substrate,which has properties similar to a sponge when wetted (with minimal or noswelling of the collagen), may absorb shielding materials, such as aliquid calcium carbonate solution. Once such a shielding solution hasbeen soaked into the collagen substrate, a sealing layer, such as ahydrophobic polymer layer, may be overlaid on the shielding material inorder to reduce risk of leakage of the shielding solution when theinfused collagen substrate later encounters moisture (e.g., either bypreventing moisture from being absorbed by the collagen or preventingleakage of the shielding solution from wetted collagen). In otherembodiments, shielding materials (e.g., particles and/or solutions) maybe interspersed within a shielding layer substrate in other matters,such as by placing particulars of shielding materials atop a substrateand then heating the substrate to allow the shielding materials to movewithin the substrate. Any other method of embedding shielding materialsand/or solutions is also contemplated. In one embodiment, a shieldinglayer including interspersed metallic particles may entirely orsubstantially avoid heating issues that would otherwise be created by,for example, MRI-induced heating. In some embodiments, shieldingmaterials may be introduced into only a portion of a shielding materialsubstrate, such as into a top 2 mm portion of a collagen substratehaving a total thickness of 4 mm, such that the lower 2 mm of thecollagen substrate do not include shielding materials and, therefore,provide primarily spacing and/or absorption to the shielding materialsinfused portion of the substrate.

In the example of FIG. 4E, the isolation sheet comprises a singleshielding layer having a thickness of between 0.05-1 mm. In theembodiment of FIG. 4F, the shielding layer has a thickness of between0.4-2.0 mm, and is adjacent a collagen layer having a thickness ofbetween 0.4-2.0 mm. The example isolation sheet of FIG. 4G includessimilar components as FIG. 4F (perhaps with varying thicknesses ofcomponents within the provided thickness ranges), but with the collagenlayer configured for placement onto radioactive carriers and providing aspacing between the radioactive carriers and the shielding layer. In theexample isolation sheet of FIG. 4H, two shielding layers, each having athickness of between 0.05-1.0 mm (perhaps different thicknesses) areplaced between collagen layers having thicknesses of between 0.05-1.0 mm(perhaps different thicknesses).

FIG. 4I illustrates an isolation sheet having a uniform compositionshielding layer 494 (e.g., one of the shielding materials discussed withreference to FIGS. 4A-4D, such as a foil) and a dispersed compositionshielding layer 496 (e.g., one of the shielding materials discussed withreference to FIGS. 4E-4H or FIGS. 7B-7I), with the combination ofshielding layers between collagen layers 492 and 498. In thisembodiment, the collagen layer 498 that is placed next to theradioactive carriers has a thickness of between 1.0-10 mm, while theopposite collagen layer 492 has a thickness of between 0.4-2.0 mm. Asdiscussed elsewhere, such layer thicknesses, placement of shieldinglayers within isolation sheets, and combinations of shielding layerswithin isolation sheets, are provided as examples—isolation sheets mayinclude various combinations of these elements.

FIG. 5 illustrates an example of manufacturing an isolation sheet. Othermethods of manufacturing isolation sheets having varying layerthicknesses, materials, radioactive shielding properties, etc., are alsocontemplated. In the example of FIG. 5, a collagen layer is initiallyformed, such as by spraying a layer of collagen onto a supportingsubstrate. Next, after the collagen layer is dried, a shielding layer isplaced on the collagen. For example, a thin layer of high Z foil may beplaced on the collagen or a shielding material may be sprayed onto thecollagen to form the shielding layer. Finally, in the example of FIG. 5,another collagen layer is formed on top of the shielding layer, such asby spraying another layer of collagen or placing preformed collagen onthe shielding layer. Another example manufacturing process that may beused to forming shielding layers is vacuum forming, which may be used toforce a collagen spray or layer against shielding materials in order toembed the shielding materials into the collagen layer. For example,shielding materials may be placed on the vacuum forming device (eitherdirectly or on a substrate layer, such as collagen) and then collagen issprayed over the shielding materials (or a collagen substrate is placedon over the shielding materials), followed by applying the vacuum forcein order to pull the collagen layer over the shielding materials, suchas while sprayed collagen dries, in order to embed the shieldingmaterials into the collagen. A similar fabrication process may be usedwith polymer and other bio-compatible substrates, rather than collagen.

FIG. 6 illustrates an isolation sheet 610 configured to providebackscatter properties that return radioactive particles into atreatment area of tissue. In some applications, the amount of radiationdelivered to a desired treatment area may be increased using anappropriately configured isolation sheet, such as the isolation sheet610, for example. Isolation sheet 610 includes a thin collagen layer616, such as having a thickness of between 0.1-1.0 mm adjacent ashielding layer 614 having radiation reflective properties, such as highZ materials. The high Z shielding layer 614 may have a thickness ofbetween 0.05-2.0 mm or more, and the thickness may be configured to meetclinical need (and/or other shielding goals discussed herein), such asby software that generates the shielding specifications. In determiningthe shielding specifications, components of the radioactive carriers maybe adjusted to provide the desired amount of radiation to the treatmentarea, considering the additional radioactive treatment provided bybackscatter of particles that are reflected back towards the treatmentarea by the high Z shielding material of the shielding layer 614. Inother embodiments, multiple high Z shielding layers may be included,such as shielding layers comprising high Z materials that have varyingbackscatter properties, such that a combination of the shieldingmaterials provides increased backscatter. In the example of FIG. 6, theisolation sheet 610 includes a collagen layer atop the high Z material.

Additional Example Shielding Materials

FIG. 7A illustrates three example shielding materials that may be usedin various embodiments of shielding layers and corresponding isolationsheets discussed herein. In particular, FIG. 7A illustrates a rod 702, acylinder 704, and a bar 706. Each of these shielding materials, as wellas any other shielding material discussed herein, may be used alone, orin conjunction with other shielding materials as part of an isolationsheet.

The rod 702 and cylinder 704 are each generally cylindrical in shape andmay have diameters of from 0.01 mm to 2 mm or more in variousembodiments. The rod 702 comprises a solid material, such as any of themetallic or nonmetallic shielding materials discussed herein, while thecylinder 704 includes a cylindrical aperture extending along a length ofthe cylinder 704. The rod 702 may be referred to as a wire 702 also,especially for smaller diameters. The bar is generally a rectangularprism shape and may be a solid shielding material (as shown in FIG. 7A)or having an elongate aperture along the length of the bar 706. The bar706 s, as well as foils that are discussed herein, may have a thicknessfrom 0.005 mm to 0.5 mm, a width of from 0.1 mm to 10 mm, and a lengthof more than 10 mm, as needed for the particular application (e.g.,according to the particular dosimetric plan). In some implementations,cylinders are hollow, while in others the cylinders are packed with air,fluid, or another solid material, such as to better meet the shieldinggoals. As noted elsewhere herein, these example shielding materials areexemplary only and do not limit the scope of other shapes, sizes,materials, configurations, etc. of other shielding materials that may beused alone or in the various isolation sheet embodiments discussedherein.

Length of the rod 702, cylinder 704, or bar 706 may vary based on theparticular dosimetric plan, such as to provide a prescribed amount ofradiation shielding, to allow flexibility sufficient for placement ofthe resultant isolation sheet (e.g., according to the dosimetric plan),and/or to reduce imaging artifacts and/or heating of the isolationsheet. For example, in order to achieve one or more of these goals,multiple shielding materials, such as rods 702, cylinders 704, and/orbars 706, may be fabricated (or sized after fabrication) to a lengththat is some fraction of a total length of a shielding layer in whichthe rods 702 will be placed (e.g., in a shielding layer substrate), suchthat the multiple rods shielding materials may be spaced apart in theshielding layer to reduce heat generation, for example.

The shielding materials may be used without a substrate, such as byadhering the rod 702 (or cylinders 704, or bars 706, etc.) with aplurality of other similar rods 702 (e.g., using one or more sutures orother biocompatible material to hold the multiple rods next to oneanother) in order to provide radiation shielding according to apatient's treatment plan. In other embodiments, the shielding materials(e.g., the rod 702, cylinder 704, bar 706, and/or other shieldingmaterials discussed herein), either alone or in combination with othershielding materials, may be embedded or adhered to a shielding materialsubstrate, such as collagen or another biocompatible material, to form ashielding layer.

Additional Example Isolation Sheets

FIGS. 7B-7I provide additional examples of isolation sheets that may bemanufactured for use in multiple dosimetric plans and/or may becustomize for a particular dosimetric plan. Such customization may beprovided by the manufacturer of the isolation sheets and/or may beimplemented by a user of the isolation sheets, such as by a surgeon orhis staff, in order to better meet the needs of a patient. For example,in some embodiments size of the isolation sheets is adjustable, such asby cutting an isolation sheet with scissors. In some embodiments,isolation sheets include markings that indicate locations of theisolation sheet that are best for cutting (in order to reduce size ofthe isolation sheet). For example, a grid pattern may be printed on atop surface of an isolation sheet to indicate spaces between shieldingmaterial embedded within one or more shielding layers of the isolationsheet.

In some embodiments, the combination of shielding materials (e.g., rodsvs. cylinders vs dots, etc., as well as dimensions of the shieldingmaterials, such as width, diameter, length, cross-sectional profile,etc.), material of the shielding materials (e.g., high-Z material vs.polymer material), and/or pattern of the shielding materials within asubstrate of an isolation sheet may be selected in order to provide atleast the minimum radiation shielding called for in the dosimetric plan,to meet clinical needs of the patient, and/or to meet radiationshielding goals, such as reducing imaging distortion and RF heating ofthe isolation sheet to a point where imaging of the treatment area ofthe patient is not effective and/or the isolation sheet puts the patientat risk of burning. Other factors, such as malleability of the isolationsheet, especially with reference to a treatment cavity that requiressignificant reshaping of an isolation sheet, may be considered indetermining these various attributes of an isolation sheet. Suchfactors, which may be referred to herein as goals, may be included in atreatment plan of a patient (e.g., a dosimetric plan developed by aradiation oncologist), may be determined or adjusted by otherphysicians, such as the surgeon, in order to meet clinical needs of thepatient (e.g., at the time of placement of the isolation sheet), and/ormay be determined to meet hospital, municipal, government, and/orpatient requirements. In some embodiments, shielding specifications,such as those discussed above, are automatically determined by softwareexecuting on a computing system, which considers various shielding goals(e.g., provided by a user or set to default minimum requirements), aswell as patient characteristics (e.g., tumor area, cavity dimensions,vital organs or other areas near the tumor area, medical images of thepatient, patient history, etc.) in determining shielding specificationsfor the patient.

In some embodiments, shielding materials (e.g., rods, bars, dots, etc.)are sized and positioned in one or more shielding layers of an isolationsheet to line up with radiation sources onto which the isolation sheetis to be placed. In such embodiments, each shielding material mayprovide direct blocking of radiation for a particular radiation source.In other embodiments, the shielding materials on an isolation sheet maynot directly correspond to and/or line up with the underlying radiationsources. Examples of various configurations of such isolation sheets areprovided below.

The various views of the example isolation sheets (e.g., top, side, andend views) represent relative relationships between shielding materialswithin one or more shielding layers, and are not necessarily to scalewith one another.

FIGS. 7B-7I each illustrates multiple views of example isolation sheets,including top view, one or more side views, and one or more end views.In other embodiments, the isolation materials illustrated may be spaceddifferently than illustrates, such as to provide additional shielding ofone portion of the isolation sheet over another portion of the isolationsheet. The example isolation sheets are illustrated with reference tocorresponding shielding layer substrates (e.g., substrate 701 of FIG.7B), which may comprise any available substrate, such as collagen orother biocompatible material in which the shielding materials areembedded. In other embodiments, the shielding layer substrate does notembed the shielding materials, but holds the shielding materials infixed positions with reference to one another. For example, a shieldinglayer substrate may comprise an adhesive backed substrate (e.g., a sheetof paper with a biocompatible adhesive on one side) onto which themultiple shielding materials are adhered and held into place withreference to one another. As discussed elsewhere herein, multipleshielding layers using various shielding layer substrates may be used incombination in various isolation sheets.

In the example isolation sheet of FIG. 7B, multiple rods 713 are spaceduniformly with reference to one another in a shielding layer substrate711. In this example, the rods 713 are arranged in seven rows and fivecolumns, with an equal space between each row and an equal space betweeneach column. In other embodiments, any other number of rows, columns, orother arrangement of rods, may be used, such as to meet one or morerequirements of a patient's treatment plan. As shown in the sidecross-section view 712, the rods are centered within the shielding layersubstrate 711. However, in other embodiments, the rods may be offsetwithin the shielding layer substrate 711, such as to provide more (orless) spacing between the radiation sources (e.g., carriers loaded withradioactive seeds) and the shielding materials. In this example, therods have a substantially circular cross-section, as shown in view 714,but in other embodiments rods 713 may have varying cross-sectionalprofiles, such as triangular, pentagon hexagonal, etc.

In the example isolation sheet of FIG. 7C, multiple cylinders 723 arespaced uniformly with reference to one another in a shielding layersubstrate 721. In this example, the cylinders 723 are arranged in sevenrows and five columns, with an equal space between each row and an equalspace between each column. In other embodiments, any other number ofrows, columns, or other arrangement of cylinders, may be used, such asto meet one or more requirements of a patient's treatment plan. As shownin the side cross-section view 722, the cylinders are centered withinthe shielding layer substrate 721. However, in other embodiments, thecylinders may be offset within the shielding layer substrate 721, suchas to provide more (or less) spacing between the radiation sources(e.g., carriers loaded with radioactive seeds) and the shieldingmaterials. In this example, the cylinders have a substantially circularcross-section and a cylindrical aperture extending through a length ofthe cylinders, as shown in view 724. In other embodiments, cylinders(e.g., the outer surface of the cylinders 723) and/or the aperture ofthe cylinders (e.g., the inner surface of the cylinders 723) may havevarying cross-sectional profiles, such as triangular, pentagonhexagonal, etc.

In the example isolation sheet of FIG. 7D, multiple bars 733 are spaceduniformly with reference to one another in a shielding layer substrate731. In this example, the bars 733 are arranged in seven rows and fivecolumns, with an equal space between each row and an equal space betweeneach column. In other embodiments, any other number of rows, columns, orother arrangement of bars, may be used, such as to meet one or morerequirements of a patient's treatment plan. As shown in the sidecross-section view 732, the bars are centered within the shielding layersubstrate 731. However, in other embodiments, the bars may be offsetwithin the shielding layer substrate 731, such as to provide more (orless) spacing between the radiation sources (e.g., carriers loaded withradioactive seeds) and the shielding materials. In this example, thebars have a substantially rectangular cross-section, as shown in view734. In other embodiments, bars may have varying cross-sectionalprofiles, such as triangular, pentagon hexagonal, etc.

In some embodiments, shielding materials (e.g., rods, bars, dots, etc.)are sized and positioned in one or more shielding layers of an isolationsheet to line up with radiation sources onto which the isolation sheetis to be placed. For example, the multiple bars 733 in the exampleisolation sheet of FIG. 7D may be arranged to correspond to positions ofradiation sources (e.g., carriers with radioactive seeds) placed on ornear a treatment surface. In this example, this 5×7 set of bars 733 maycorrespond to a 5×7 set of radiation sources placed in a tumor cavity.Thus, shielding of direct radiation from the radiation sources (e.g.,perpendicular to orientation of a seed placed in a horizontalorientation, such as in FIG. 1A-1C) may be most significantly shielded,while radiation emitted at an angle from the radiation sources (e.g.,between 60-80 degrees from the longitudinal axis of the seed) may not beshielded as significantly. However, this spaced positioning of theshielding materials to match up with (or “mirror”) the underlyingradiation sources may provide sufficient overall shielding (e.g., reducethe amount of radiation by more than 25%, 50%, 75%, 90%, or to someacceptable amount of radiation (for example, measures in gray (Gy)) andalso provide improved imaging of the patient's anatomy below theshielding materials and/or reduce risk of RF heating (e.g., due to thespaces between the shielding materials). Accordingly, such a one-to-onecorrespondence of individual shielding materials with individualradiation sources may best meet the shielding goals for some clinicaluses. Similarly, a one-to-many relationship of spaced apart shieldingmaterials to radiation sources may provide similar advantages in view ofspacing between the shielding materials. For example, with reference toFIG. 7E (discussed further below), each of the 7 elongate rods 743 maycorrespond to (and be aligned with when placed thereon) multipleradiation sources. For example, each of the elongate rods 743 maycorrespond to 5 radiation source, such as tiles with embedded seeds,such that the isolation sheet 740 provides shielding of 35 radiationsource (5 radiation sources in 7 rows). As discussed herein, radiationsource placement within a tumor cavity may be irregular, e.g., not is arigid row and column arrangement, and, thus, the shielding materials ofan isolation sheet may be arranged in a similar irregular arrangement(either based on the dosimetry plan, surgeon's, or other description ofplanned arrangement of the radiation sources and/or based on actualarrangement of the radiation sources, such as at the time ofimplantation) of the radiation sources in order to provide similardirect shielding of the radiation sources, while providing some spacingbetween the shielding materials.

In the example isolation sheet of FIG. 7E, multiple rods 743 are spaceduniformly with reference to one another in a shielding layer substrate741. In this example, the rods 743 are elongate to extend across a largeportion of the substrate 741 width, such as 90%, 95%, 99% or more. Inthis example, the rods 743 are arranged in seven rows and a singlecolumn, with an equal space between each row. In other embodiments, anyother number of rows, or other arrangement of rods, may be used, such asto meet one or more requirements of a patient's treatment plan. Forexample, a shielding layer substrate having an area of 2.5 cm×2.5 cmmight achieve similar shielding of radiation though use of 10 rodshaving diameters of 2 mm (with about 0.5 mm space between the rods) and100 rods having diameters of 0.02 mm (with about 0.005 mm space betweenthe rods). However, one or more of various attributes of the shieldinglayer may differ between the two arrangements (and quantities) of rods.For example, the shielding layer with 100 rods may provide greatermalleability, but increase heating and imaging artifacts, compared tothe shielding layer with 10 rods. As shown in the side cross-sectionview 742, the rods are centered within the shielding layer substrate741. However, in other embodiments, the rods may be offset within theshielding layer substrate 741, such as to provide more (or less) spacingbetween the radiation sources (e.g., carriers loaded with radioactiveseeds) and the shielding materials. In this example, the rods withvarious cross-sections profiles are shown in end view 744. In someembodiments, cross-sectional profile of the rods may be selected basedon radiation shielding, imaging artifact potential, heating potential,malleability, availability, cost, and/or other factors associated withthe various rod shapes. For example, cross-sectional end view 744Dillustrates rods having a generally hemispherical shape, which mayprovide increased malleability and reduced heating when compared tocertain other cross-sectional profiles, such as circular or rectangular.

In the example isolation sheet of FIG. 7F, two sets of bars 753 and 755are arranged in layers of the shielding layer substrate 751, such as toprovide additional radiation blocking and/or absorption. In thisexample, multiple bars 753 are spaced uniformly in rows in an upperportion of the substrate 751 with a second set of multiple bars 755spaced uniformly in columns in a lower portion of the substrate 751, asshown in side cross sectional view 752. As with other exampleembodiments discussed herein, the quantity, size, and spacing of thebars 753, 755 may vary from the configuration illustrated, such as toinclude a larger quantity and smaller size of bars (see example FIG. 7E,above). As shown in the side cross-section view 752, the bars 753 arespaced from the bars 755. In other embodiments, the bars may be spacedfurther or closer from one another. In this example, the bars have asubstantially rectangular cross-sectional views 752 and 754. In otherembodiments, bars may have varying cross-sectional profiles, such astriangular, pentagon hexagonal, etc.

In the example isolation sheet of FIG. 7G, a mesh of shielding materials763 embedded in a shielding layer substrate 761 is illustrated. Theshielding materials 763 may be formed in the mesh pattern by amanufacturer (e.g., of the mesh pattern of shielding materials 763 or ofthe substrate pre-loaded with the shielding materials 763) or by asurgeon, for example, prior to implantation of the radioactive sources.In various embodiments, the multiple vertical and horizontal shieldingmaterials may be in various shapes, such as bars, rods, wires,cylinders, etc. In the particular example of FIG. 7G, the shieldingmaterials each have a substantially square cross-sectional shape, asillustrated in side view 762 and end view 764. In other embodiments, thevertical and horizontal shielding materials may have different shapes,sizes, cross-sectional profiles, etc. As with other example embodimentsdiscussed herein, the quantity, size, and spacing of the shieldingmaterials 763 may vary from the configuration illustrated, such as toinclude a larger quantity and smaller size of shielding materials. Asshown in the cross-sectional views 762 and 764, the shielding materials763 are centered within a height of the substrate 761. In otherembodiments, the shielding materials may be closer to a top (or bottomsurface).

FIG. 7H illustrates an isolation sheet 766 including shielding materials763 woven into a mesh pattern within a substrate layer 768. In otherembodiments, such as mesh shielding material formed in this, or other,mesh patter may not be included in a substrate layer, such as becausethe intertwining of the substrate materials to form the mesh may providesufficient adherence between the shielding materials to remove need fora separate substrate. In the embodiment of FIG. 7H, the shieldingmaterials may comprise rods, wires, or other shielding materials, thatare pre-formed by a manufacturer in the mesh pattern illustrated in sidecross section 769A and end cross section 769B, or another mesh pattern.

In the example isolation sheet of FIGS. 7I & 7J, multiple dots (orspheres) 773 and 783 are illustrated in different configurations withinshielding layer substrates 771 and 781. In particular, dots 773 of FIG.7I are positioned with the dots align in multiple rows and columns, asshown in the various views 770, 772, and 774. In FIG. 7J, however, thedots 783 are positioned in columns (and rows) such that dots in adjacentcolumns (and rows) are offset from one another, as shown in sidecross-sectional views 782 and 784. Such an offset spacing may provideone or more of various advantages over uniformly spaced dots, such asgreater radiation shielding with a comparable quantity of equivalentdots. As shown in the side cross-sectional views 772 and 782, the dotsare centered within the shielding layer substrates 771 and 781,respectively. However, in other embodiments, the dots may be offsetwithin the shielding layer substrates 771 and 781, such as to providemore (or less) spacing between the radiation sources (e.g., carriersloaded with radioactive seeds) and the dots. In other examples, othershielding materials, such as rods, cylinders, etc., may be positioned inan offset pattern similar to illustrated in FIG. 7J.

In the example isolation sheet of FIG. 7L, cross-sectional side view 796and end view 798 illustrate multiple rows of rods. In this example, anupper portion of the isolation sheet includes a set of parallel rodsacross a width of a shielding layer substrate, followed by a set ofparallel rods that are each perpendicular to the upper row of rods, andthen additional rows and columns of rods. As with other exampleembodiments discussed herein, the quantity, size, spacing, quantity oflayers, etc. of the rods (and/or other shielding materials used as analternative, or addition, to rods) may vary from the configurationillustrated.

FIG. 8 illustrates an example isolation sheet 800 adjacent radioactiveseeds in a substrate 801. In this example, multiple parallel rods arepositioned in an upper portion of the substrate 801, while multiple rowsand columns of radioactive seeds 803 are positioned in a lower portionof the substrate 801. Thus, the composite isolation sheet 800 mayreplace the need for multiple radiation sources (e.g. hot carriers) anda separate isolation sheet, saving the treatment planning staff,surgeon, and possibly the patient, time and effort in implementation ofthe treatment plan. Additionally, this configuration may increaseaccuracy of a treatment plan by ensuring that the radiation sources arein a proper configuration with reference to one another, and also byensuring that the desired shielding is properly aligned with theradiation sources.

Other Embodiments

Conditional language, such as, among others, “can,” “could,” “might,” or“may,” unless specifically stated otherwise, or otherwise understoodwithin the context as used, is generally intended to convey that certainembodiments include, while other embodiments do not include, certainfeatures, elements and/or steps. Thus, such conditional language is notgenerally intended to imply that features, elements and/or steps are inany way required for one or more embodiments or that one or moreembodiments necessarily include logic for deciding, with or without userinput or prompting, whether these features, elements and/or steps areincluded or are to be performed in any particular embodiment.

It should be emphasized that many variations and modifications may bemade to the above-described embodiments, the elements of which are to beunderstood as being among other acceptable examples. All suchmodifications and variations are intended to be included herein withinthe scope of this disclosure. The foregoing description details certainembodiments of the invention. It will be appreciated, however, that nomatter how detailed the foregoing appears in text, the invention can bepracticed in many ways. As is also stated above, the use of particularterminology when describing certain features or aspects of the inventionshould not be taken to imply that the terminology is being re-definedherein to be restricted to including any specific characteristics of thefeatures or aspects of the invention with which that terminology isassociated. The scope of the invention should therefore be construed inaccordance with the appended claims and any equivalents thereof.

What is claimed is:
 1. A shielding apparatus comprising: a substrate;and a plurality of shielding materials positioned within the substrateat positions substantially matching positions of a correspondingplurality of radiation sources, at least some of the radiation sourcesarranged with gaps between the at least some of the radiations sourcesand adjacent of the plurality of radiation sources; wherein theapparatus is adapted for placement on the plurality of radiation sourcesso that each of the shielding materials provides substantial shieldingof radiation emitted by a corresponding radiation source.
 2. Theshielding apparatus of claim 1, wherein gaps comprise collagen of thesubstrate between shielding materials.
 3. The shielding apparatus ofclaim 1, wherein substantial shielding shields more than 80% ofradiation.
 4. The shielding apparatus of claim 1, wherein the shieldingmaterials are formed in the shape of rods, cylinders, or spheres.
 5. Theshielding apparatus of claim 1, wherein a dosimetric plan indicates x*yradiation sources arranged in x rows and y columns, and the substrate isembedded with x*y shielding materials in x rows and y columns.
 6. Theshielding apparatus of claim 5, wherein the dosimetric plan indicates agap distance between adjacent radiation sources in each of the x rows,and the shielding materials in each of the x rows are spaced apart bythe gap distance.
 7. The shielding apparatus of claim 6, wherein thedosimetric plan indicates a second gap distance between adjacentradiation sources in each of the y columns, and the shielding materialsin each of the y columns are spaced apart by the second gap distance. 8.The shielding apparatus of claim 1, wherein a dosimetric plan indicatesan irregular arrangement of the plurality of radiation sources, and theshielding materials are positioned in the same irregular arrangement inthe substrate.
 9. The shielding apparatus of claim 1, wherein theshielding apparatus is sufficiently malleable to be formed into asubstantially hemispherical shape within a corresponding substantiallyhemispherical cavity.
 10. The shielding apparatus of claim 1, whereinthe substrate is adhered to a bio-compatible material.
 11. The shieldingapparatus of claim 1, wherein substantial shielding shields more than50% of radiation.
 12. An apparatus comprising: a substrate including: aradiation layer comprising a plurality of radiation sources positionedwithin the substrate, at least some of the radiation sources arrangedwith gaps between the at least some of the radiations sources; and ashielding layer comprising a plurality of shielding materials positionedwithin the substrate at positions substantially matching positions ofradiation sources; wherein the shielding layer is adapted to providesubstantial shielding of radiation emitted by radiation layer.
 13. Theapparatus of claim 12, wherein the shielding materials are formed in theshape of rods, cylinders, or spheres.
 14. The apparatus of claim 12,wherein the plurality of radiation sources are arranged into x rows andy columns within the radiation layer.
 15. The apparatus of claim 12,wherein the plurality of shielding materials are arranged into x rowsand y columns within the shielding layer.
 16. The apparatus of claim 12,wherein substantial shielding shields more than 50% of radiationincident on the shielding layer.
 17. The apparatus of claim 16, whereinthe shielding layer reflects radiation towards the radiation layer. 18.The apparatus of claim 12, wherein a first shielding material of theplurality of shielding materials is positioned within the shieldinglayer to provided substantial shielding to a plurality of radiationsources in the radiation layer.
 19. The apparatus of claim 18, whereinthe first shielding material comprises an elongated rod.
 20. Amanufacturing method comprising: positioning a plurality of shieldingmaterials within a shielding substrate at positions substantiallymatching a corresponding plurality of radiation sources within aradiation substrate, at least some of the radiation sources arrangedwith gaps between the at least some of the radiation sources; whereinthe shielding materials are adapted to provide substantial shielding ofradiation emitted by corresponding radiation sources.
 21. Themanufacturing method of claim 20, wherein the shielding substrate andradiation substrate are layers of a biocompatible material.
 22. Themanufacturing method of claim 21, wherein the biocompatible material iscollagen.